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Effect of a single injection of humanized anti-CD154 monoclonal antibody on the platelet-specific autoimmune response in patients with immune thrombocytopenic purpura

Kuwana, Masataka ; Nomura, Shosaku ; Fujimura, Kingo ; Nagasawa, Toshiro ; Muto, Yoshitomo ; Kurata, Yoshiyuki ; Tanaka, Shigeru ; Ikeda, Yasuo

Blood, 2004-02, Vol.103 (4), p.1229-1236 [Periódico revisado por pares]

Washington, DC: Elsevier Inc

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Título:
Effect of a single injection of humanized anti-CD154 monoclonal antibody on the platelet-specific autoimmune response in patients with immune thrombocytopenic purpura
Autor: Kuwana, Masataka ; Nomura, Shosaku ; Fujimura, Kingo ; Nagasawa, Toshiro ; Muto, Yoshitomo ; Kurata, Yoshiyuki ; Tanaka, Shigeru ; Ikeda, Yasuo
Assuntos: Adult ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal, Humanized ; B-Lymphocytes - immunology ; Biological and medical sciences ; Blood Platelets - immunology ; CD40 Ligand - immunology ; Female ; Hematologic and hematopoietic diseases ; Humans ; Lymphocyte Count ; Lymphocyte Subsets ; Male ; Medical sciences ; Middle Aged ; Platelet Count ; Platelet diseases and coagulopathies ; Platelet Glycoprotein GPIIb-IIIa Complex - immunology ; Purpura, Thrombocytopenic, Idiopathic - immunology ; Purpura, Thrombocytopenic, Idiopathic - therapy ; T-Lymphocytes - immunology
É parte de: Blood, 2004-02, Vol.103 (4), p.1229-1236
Descrição: Blockade of the CD40/CD154 signal is a potential immunomodulatory strategy for T-cell–mediated diseases. As a part of a phase 1, multicenter, dose-escalating trial of humanized monoclonal antibody to CD154 (IDEC-131/E6040) in patients with refractory immune thrombocytopenic purpura (ITP), the autoimmune response to glycoprotein IIb/IIIa (GPIIb/IIIa) was evaluated at successive time points. Five patients each were given a single infusion of 1, 2, 5, or 10 mg/kg IDEC-131/E6040 and followed for 3 months. All adverse events were mild, and there were no severe infections or thromboembolic events. No increase in platelet count was observed in patients treated at 1, 2, or 5 mg/kg, but an increase was observed in 3 patients treated at 10 mg/kg. In only the patients treated at 5 or 10 mg/kg, the frequency of B cells producing anti-GPIIb/IIIa antibodies, GPIIb/IIIa-induced T-cell proliferation, and anti-GPIIb/IIIa antibody production by antigen-dependent T–B-cell collaboration were all suppressed in parallel after the treatment, with a slow return to baseline. In contrast, T-cell response to an irrelevant antigen was not affected. These findings suggest that CD40/CD154 blockade therapy is potentially effective for refractory ITP, through selective suppression of autoreactive T and B cells to platelet antigens.
Editor: Washington, DC: Elsevier Inc
Idioma: Inglês

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Effect of a single injection of humanized anti-CD154 monoclonal antibody on the platelet-specific autoimmune response in patients with immune thrombocytopenic purpura

Kuwana, Masataka ; Nomura, Shosaku ; Fujimura, Kingo ; Nagasawa, Toshiro ; Muto, Yoshitomo ; Kurata, Yoshiyuki ; Tanaka, Shigeru ; Ikeda, Yasuo

Washington, DC: Elsevier Inc

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